A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.
A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.
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DOI：
10.1056/nejmoa2033130
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发表时间：
2021-03-11
期刊：
影响因子：
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通讯作者：
Neaton JD
中科院分区：
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作者：
ACTIV-3/TICO LY-CoV555 Study Group;Lundgren JD;Grund B;Barkauskas CE;Holland TL;Gottlieb RL;Sandkovsky U;Brown SM;Knowlton KU;Self WH;Files DC;Jain MK;Benfield T;Bowdish ME;Leshnower BG;Baker JV;Jensen JU;Gardner EM;Ginde AA;Harris ES;Johansen IS;Markowitz N;Matthay MA;Østergaard L;Chang CC;Davey VJ;Goodman A;Higgs ES;Murray DD;Murray TA;Paredes R;Parmar MKB;Phillips AN;Reilly C;Sharma S;Dewar RL;Teitelbaum M;Wentworth D;Cao H;Klekotka P;Babiker AG;Gelijns AC;Kan VL;Polizzotto MN;Thompson BT;Lane HC;Neaton JD
LY-CoV 555是一种中和性单克隆抗体，与2019冠状病毒病（Covid-19）门诊患者的病毒载量和住院或急诊频率下降相关。需要有关该抗体对因Covid-19住院的患者的影响的数据。在这项治疗药物的平台试验中，我们以1：1的比例随机分配了患有新冠肺炎但没有终末器官衰竭的住院患者，接受LY-CoV 555或匹配的安慰剂。此外，所有患者都接受了高质量的支持性治疗作为背景治疗，包括抗病毒药物remdesivir，以及在有指征时补充氧气和糖皮质激素。LY-CoV 555（剂量为7000 mg）或安慰剂在1小时内单次静脉输注给药。主要结局是在90天内持续恢复，如至事件发生时间分析所评估。在第5天，根据肺功能的7类顺序量表进行中期无效评估。2020年10月26日，在314例患者（LY-CoV 555组163例，安慰剂组151例）接受随机化和输注后，数据和安全性监测委员会建议停止无效入组。自症状发作以来的中位间隔时间为7天（四分位距，5至9）。在第5天，LY-CoV 555组共有81名患者（50%），安慰剂组共有81名患者（54%）处于肺部结局的两个最有利类别之一。在7个类别中，LY-CoV 555组比安慰剂组更有利的优势比为0.85（95%置信区间[CI]，0.56至1.29; P=0.45）。LY-CoV 555组和安慰剂组发生主要安全性结局（死亡、严重不良事件或临床3级或4级不良事件的复合终点）的患者百分比相似（分别为19%和14%;比值比为1.56; 95%CI为0.78至3.10; P=0.20）。持续恢复的率比为1.06（95% CI，0.77 - 1.47）。单克隆抗体LY-CoV 555与Remdesivir联合给药时，在没有终末器官衰竭的Covid-19住院患者中没有显示出疗效。（由Operation Warp Speed和其他人资助; TICO ClinicalTrials.gov编号，NCT 04501978。
LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P=0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P=0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.)